ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

One case of de novo donor specific antibody(dnDSA)mediated rejection after pediatric kidney transplantation(KT)was analyzed retrospectively.The risk factors and prevention procedures associated with dnDSA induction, and the clinical features and protocols for late post-transplant antibody-mediated rejection(AMR)in pediatric patients were presented.

Objective:To summarize and analyze the clinical treatment of aspergillus infection in the central nervous system.Methods:Data was obtained from a recipient who were diagnosed with invasive aspergillosis in the central nervous system after liver transplantation.We retrospectively analyzed the clinical character of the recipient." Liver transplantation" , " Aspergillus" , " brain" and " aspergillus" were searched for literature published in English or Chinese in Wanfang data, CNKI and PubMed database for nearly 5 years until January 2022.Results:A 33 years old recipient was admitted to the hospital with fatigue, chest distress and shortness of breath after liver transplantation on postoperative day(POD)48.On the computed tomography(CT)scan of the chest, multiple exudative lesions was observed in both lungs.Multiple sputum cultures were grown as Candida albicans.The symptoms of chest tightness and shortness of breath were significantly improved by treating with caspofungin compared before.On POD 79, the recipient developed stubborn nausea and vomiting.Cranial enhanced magnetic resonance imaging(MRI)showed central nervous system(CNS)infection.Numerous traditional pathogenic microorganisms tests of cerebrospinal fluid(CSF)were all negative.With the help of metagenomics next generation sequencing(mNGS), aspergillus fumigatus was detected in CSF.The recipient received therapy with voriconazole and rehabilitation.Therapy with voriconazole was continuous for 8 months.Unfortunately, the recipient developed cholestasis due to repeated biliary infection and eventually died of liver failure 13 months later.Conclusions:Although the mortality rate of aspergillus infection in the central nervous system is very high after liver transplantation, timely and effective treatment is still expected to improve its prognosis.

Objective:To summarize the clinical outcomes of en-bloc kidney transplantation from small infant donors to adult recipients at a single center.Methods:A total of 22 en-bloc transplantations from pediatric donors to adult recipients were performed from July 2013 to October 2017 in Institute of Organ Transplantation Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science. Clinical data were retrospectively analyzed. The average age of 22 donors was (2.9±1.7) months with an average weight of (4.9±1.4) kg and 15 of them were aged under 3 months. The average weight of 22 adult recipients was (46.3±5.6) kg and most recipients were female. The causes of early graft failure and recipient death were examined during follow-ups. The recipients with functioning grafts post-transplantation were divided into single kidney survival group and en-bloc kidney survival group based upon the occurrence of unilateral vascular thrombosis. Medium/long-term renal graft function was compared between two groups.Results:Early graft failure occurred in 4 recipients. The causes were bilateral renal vascular thrombosis ( n=2), renal rupture ( n=1) and multiple organ failure followed by death ( n=1). Eighteen recipients were discharged after a recovery of renal graft function. One case had a removal of bilateral renal grafts due to new-onset graft tumor and another two died from interstitial pneumonia and complicate systematic disorder respectively during follow-ups. Among the remaining 15 recipients, 10 achieved bilateral renal survival (median follow-up: 59 months) and 5 unilateral renal survival (median follow-up: 48 months). The average eGFR of bilateral renal survival group was significantly higher than that of unilateral renal survival group at Year 1 post-transplantation (95±27 vs 61±24 ml/min/1.73 m 2, P<0.05) while the gap narrowed at Year 3 and there was no statistical significance (95±21 vs 69±31 ml/min/1.73 m 2, P=0.12). Conclusions:Although en-bloc kidney transplantation from infant donors can expand organ donor pool, there is a higher risk of early graft failure and unilateral renal vascular thrombosis. Nevertheless, satisfactory renal transplant outcomes may be achieved in patients with unilateral renal graft survival.

Objective:To explore the outcome of kidney transplantation from donation after cadaveric death(DCD)with high pathological Remuzzi score.Methods:From January, 2019 to December, 2019, 31 recipients of kidney allograft transplantation from marginal donors with Remuzzi score≥4 in preimplantation biopsy were retrospectively enrolled. They were divided into two groups of dual kidney transplantation(DKT, 14 cases)and single kidney transplantation(SKT, 17 cases). Median Remuzzi score of left kidney(5.05 in DKT group vs 4.92 in SKT group)or right kidney(5.26 vs. 4.58)was comparable. Dual donor kidneys were implanted into ipsilateral iliac fossa. Survival outcomes, kidney function, acute rejection episodes, incidence of delayed graft function(DGF)and proteinuria were recorded within Year 1 post-operation.Results:Proportion of male(92.9% vs. 52.9%, P<0.05)and recipient's body mass index(BMI, 23.93 vs. 21.09)were significant higher in DKT group than those in SKT group. One graft failure occurred in DKT group at Month 11 post-operation. The 1-year graft survival rate was 92.9% in DKT group and 1-year recipient survival rate both 100% in two groups. Mean 12-month serum creatinine[SCr, (164±37.7)μmol/L vs. (154.92±96.2)μmol/L]and estimated glomerular filtration rate[eGFR, (41.84±9.01) vs. (44.8±18.16)ml/(min·1.73m 2)]were comparable between two groups(both P>0.05). There was no occurrence of thrombosis resulting in graft loss. One-year incidence of acute rejection, rate of DGF(42.9% vs 41.2%)and proteinuria(57.1% vs. 41.2%)were comparable between two groups(both P>0.05). Conclusions:Through donor-recipient matching and dual kidney transplant allocation, short-term survival outcome of kidney allograft from marginal donors with high Remuzzi score≥4 is encouraging. However, long-term outcomes should be further examined.

Objective:To summarize the transplant outcomes of pediatric kidney transplantation at a single center and discuss probable measures of improving the outcomes.Methods:A total of 111 pediatric renal transplantation were performed from September 2002 to September 2019. They were divided into adult-donor group ( n=41) and pediatric-donor group ( n=70). Adult-donor group consisted of two subgroups based upon donor sources: living-donor group ( n=19) and deceased-donor group ( n=22). Pediatric-donor group consisted of two subgroups based upon surgical types: single kidney group ( n=48) and en bloc kidney group ( n=22). Clinical data and outcomes of grafts and recipients were retrospectively analyzed. Results:The average age of recipients was (15.6±1.9) years in adult-donor group. None developed delayed graft function (DGF) in living-donor group whereas 6 patients (27.3%) had DGF in deceased-donor group ( P<0.05). During a follow-up period of 22-181 months, 1-year and 5-year graft survivals were 100% vs 94.1% and 93.8% vs 94.1% in living-donor and deceased-donor groups respectively. There were no statistical differences. In pediatric-donor group, the age of donors was significantly lower in en bloc subgroup than that in single kidney subgroup (median: 0.5 vs 6 months, P<0.05). The age of recipients was similar between two subgroups: (9.5±5.3) years in single kidney group vs. 11.5± 1.8 years in en bloc kidney group. In addition, 7 cases of single kidney were transplanted for infant recipients aged under 1 year. Vascular thrombosis occurred in 3 patients (6.3%) of single kidney group, less than that in 5 patients (22.7%) of en bloc kidney group ( P=0.06). During a follow-up period of 4-54 months, 1-year and 2-year graft survivals were 85% and 80% in single kidney group whereas 75% and 70% in en bloc kidney group. However, there was no statistically significant difference. One-year survival was 98% in single kidney group and 95% in en bloc kidney group. Conclusions:For elder pediatric recipients, excellent kidney transplant outcomes may be achieved with grafts from adult donors. For pediatric kidney recipients, transplant outcomes can be further improved with careful assessments and cautious usage of small grafts, particularly those form neonatal donors.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective To explore the influencing factors and treatment strategies of long-term survival after simultaneous pancreas and kidney transplantation (SPK ) .Methods One case of long-term post-SPK survival was reviewed and its influencing factors were analyzed along with the relevant literature .Results At 10 years post-SPK ,the patient lost transplanted kidney due to rejection and underwent secondary kidney transplantation . The transplanted pancreas functioned well and has survived for more than 18 years .Conclusions Strict preoperative screening ,adopting mature surgical approaches ,aggressive managements of various perioperative complications ,strengthening of health education of recipients ,improving of compliance and long-term regular follow-ups are conducive for enhancing long-term survival of recipients and grafts of SPK .

Objective To summarize the experience of one case of anastomotic leakage after simultaneous pancreas-kidney transplantation (SPK ) with enteric drainage .Methods One case of type 2 diabetes mellitus complicated with end-stage nephropathy undergoing SPK was retrospectively analyzed .Iliac venous systemic circulation was employed for pancreatic venous reflux ,transplanted pancreas exocrine via enteric drainage and side-to-side anastomosis between donor pancreaticoduodenum and recipient jejunum . Pancreatoduodenal anastomotic leakage occurred at 12 days post-operation .During re-operation ,Roux-en-Y anastomosis was established between donor pancreaticoduodenum and recipient jejunum .And the relevant domestic and foreign literatures were searched .Results The follow-up time was 3 month after a second operation .Recipient pancreas and kidney transplantation survived well . There was no onset of enteric leakage .The incidence of anastomotic leakage varies greatly between different transplantation centers both at home and abroad .The incidence ranged from 3 .6％ to 11 .3％ .And the risk of pancreatic loss was as high as 54 .6％ .Conclusions As a severe postoperative complication ,anastomotic fistula after SPK may cuase abdominal infection . Even after reparing enteric fistula , the risk of leakage remains high . Roux-en-Y anastomosis is other therapeutic option .

Objective To explore the relationship between cellular rejection and the development of allo-or xenografted primordia from different gestational ages .Methods Whole rat metanephroi from embryonic day E14～ E19 were transplanted into omenta of outbred (SD → SD ,6 groups ,n≥10 each ;E15-E17SDCsA ,3 groups ,n=15 each) ,syngeneic (Lewis→Lewis ,5 groups ,n=8 each) ,allogeneic (Lewis→BN ,E15BN n= 6 each E15BNCsA n= 10 each ,E16BNCsA n= 10 each) rats and xenogeneic (Lewis→C57groups ,E15C57 n=10 each ,E15C57CsA ,n=8 each ;Lewis→Balb/c nude mice ,3 groups ,n=10 each) recipients .Histopathology ,Banff's grading and electron microscopy (EM ) were utilized for assessing the graft development .Similarly ,biochemical indicators and creatinine clearances were measured .Results At 4 weeks post-transplantation , in SD → SD groups ,E14-E17SD metanephroi developed with Banff ' s rejections . E14/E15SD was significantly lighter than E16/E17SD ( P< 0 .01 );E18/E19SD barely developed . After cyclosporine A (CsA , 8 mg·kg -1·d-1 )dosing ,Banff's rejection of E15-E17SDCsA group lessened significantly .In Lewis→BN ,E15BN metanephroi were completely rejected .After dosing CsA (12 mg·kg -1·d-1 ) ,E15BNCsA and E16BNCsA Banff ' s rejections became alleviated . Upon a discontinuation of CsA , both metanephroi were rejected . In Lewis → Lewis , E15 ～ E17Lewis metanephroi developed well . No significant difference existed in Banff's classification (P>0 .05) .E14Lewis and E18Lewis rats had significantly poorly differentiated metanephroi than those in E16 Lewis group .In Lewis→C57BL/6 , E15 metanephroi were rejected at Day 14 post-transplantation (n= 10) and no improvement was evident after CsA dosing (15 mg·kg -1·d-1 ,n=8) .In Lewis→Balb/c nude mice ,all E15～E17Balb/c metanephroi developed well .Both light microscopy and EM examination showed normal nephrons and collecting ducts and wet weight ,creatinine or urea nitrogen of effusion showed no significant difference (P>0 .05) .E15Lewis and E16Lewis had significantly different values of wet weight and creatinine clearances from those of E15SDCsA and E16SDCsA .E15SDCsA had the greatest wet weight and the lowest creatinine clearance rate (P< 0 .01) .Conclusions After controlling rejection during allo-and xenotransplantations ,E15 ,E16 and E17 rat metanephros have similar development characteristics . And cellular immunogenic factors still remain the major barriers to their developments .